US3919417A - Method for decreasing the reproductive function of mammals - Google Patents

Method for decreasing the reproductive function of mammals Download PDF

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Publication number
US3919417A
US3919417A US421893A US42189373A US3919417A US 3919417 A US3919417 A US 3919417A US 421893 A US421893 A US 421893A US 42189373 A US42189373 A US 42189373A US 3919417 A US3919417 A US 3919417A
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Prior art keywords
organosilicon compound
mammals
decreasing
female
recited
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US421893A
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Donald R Bennett
James A Mchard
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Dow Silicones Corp
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Dow Corning Corp
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Priority claimed from US00837922A external-priority patent/US3830912A/en
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Priority to US421893A priority Critical patent/US3919417A/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/695—Silicon compounds
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S424/00—Drug, bio-affecting and body treating compositions
    • Y10S424/12—Fertilization attaching inhibition
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S424/00—Drug, bio-affecting and body treating compositions
    • Y10S424/14—Topical contraceptives and spermacides

Definitions

  • This invention relates to a method for altering the reproductive function of mammals.
  • a male mammal so treated exhibits depressant effects.
  • the sex accessory organos of the male can be reduced in function and/or size and, with sufficient dosage, the male can also be rendered sterile as a result of depression of testes function.
  • a female mammal so treated exhibits a decrease of fertility, i.e., the female mammals capability to conceive is inhibited with larger doses such that the female may be rendered sterile or abort if pregnant.
  • the principal object of this invention is to provide a therapeutically effective organosilicon compound which can render a male or female mammal sterile.
  • Another principal object of this invention is to provide a method of administering an organosilicon compound which can be useful in the treatment of prostatic hypertrophy.
  • This invention relates to a method for decreasing the reproductive function of mammals which comprises administering an effective amount in the range of from 100 mg. to 5,000 mg./kg. of an organosilicon compound of the formula
  • the organosilicon compound can be named as monophenylseptamethylcyclotetrasiloxane.
  • organosilicon compound noted herein can be readily prepared by well known techniques described in the literature, e.g., by the cohydrolysis of chlorosilanes or by a suitable Grignard reaction.
  • the process of the present invention is operative on any mammal, e.g., rodents such as mice, rabbits and rats; domestic animals such as cats, swine, dogs, cattle, horses, and sheep; animals wild in nature such as deer, fox, wolves and lynx; and primates such as monkeys and man.
  • rodents such as mice, rabbits and rats
  • domestic animals such as cats, swine, dogs, cattle, horses, and sheep
  • animals wild in nature such as deer, fox, wolves and lynx
  • primates such as monkeys and man.
  • organosilicon compound in any pharmacologically acceptable manner. They can be orally administered, parenterally administered or, in
  • parenteral mode of administration would, of course, include subcutaneous administration, intramuscular administration and the like.
  • organosilicon compound described herein can be administered either in pure form in or combination with a pharmaceutically acceptable carrier or diluent.
  • suitable carriers include sesame oil, corn oil, mineral oil and other well known fat soluble carriers commonly employed in numerous pharmaceutical preparations.
  • the dose range of the organosilicon compound is in a pharmacologically effective amount.
  • a dose range of from about mg. to about 5,000 mg. per kilogram of body weight has been found to be suitable; however, the precise dosage is ultimately dependent upon the mammal, the vehicle used, the route of administration, and the specific effects one wishes to achieve.
  • the organosilicon compound may be administered as a single dose or it may be administered in daily dosage over varying periods of time, e.g., from about 7 to about 30 days or more.
  • the time required to achieve the desired effect is also variable, ranging anywhere from days to weeks or months, depending upon various factors, e.g., the species of mammal, dosage, route of administration, and the specific effect one wishes to achieve.
  • the particular alteration of the reproductive function which has been observed after administering the compound of the present invention to male mammals is a decrease in sex accessory organ function (decreased seminal fluid) and size (decreased seminal vesicle) with smaller doses of the compound and a decrease in prostatic or testicular function (decreased sperm count) or size with larger doses.
  • the method ofthis invention can be useful for decreasing the size of male sex accessory organs.
  • sex accessory organs are more sensitive than the testes to the organosilicon compound so that it is possible to decrease prostatic function and size without producing a significant effect on testicular size.
  • the method of this invention can be particularly useful for the treatment of prostatic hypertrophy.
  • the compound of the formula at a daily (seven daily doses) dosage level of 100 mg. per kg. of body weight, it has been found that the prostate is significantly reduced in size.
  • the anticipated embryo may fail to form or it may be resorbed by the female mammal.
  • the percent increase in uterine weight was determined between the control (sesame oil) and the treated animals.
  • Table ll illustrates estrogen-like activity in the immature female 5 rat based upon percent increase in uterine weight. This example illustrates depressant activity of a certain Organosilicon compound in the male rat.
  • a group of male rats (Sprague Dawlcy strain) were TABLE H orally dosed via gastric intubation with an organosili- EstrogemLike Activity Ofit Certain Organosilicon con compound f h f l lO Compound in the Immature
  • Female Rat Mean Uterine Weight (gm) Uterine O 100 gm Weight Dose final 92 Group mgJkg.
  • EXAMPLE 2 (CH,), i0 i c.ii, 200 s l76.93 I87"
  • This example illustrates the estrogen-like activity of the Organosilicon compound in the immature female daily ommmingfma daywm autopsy on day Q rat. "p .0] compared to control.
  • Control 10 380 384 .00264 .00158 .001 l9 .00905 :00020 100005 :00005 $00016 (i k), Halt i-O- i i-O- iC, H,, 10 381 37l .00115 .00i00 .0007! .00860 ,1, H, 1.00019" :OOOOS" :.00006*" 100018 ratio equals organ or fluid weight (gramsflfinal body weight (grams) "daily oral dosing of I00 mgJkg. of body weight for 7 days with autopsy on day 8. '"p .00] compared to control,
  • An immature female Wistar rat was orally adminis- 50 EXAMPLE 3 tered (via gastric intubation) either 50 mg./kg. of body weight or 200 mg./kg. of body weight of an orariosilicon compound of the formula TABLE "I Group Anti-Estrogen Activity of The Organosilicon Compound in the Immature Female Rat Organosilicon Mean Uterine Weight Dose (grams)ll00 grams mgJkg.
  • This example illustrates the antifertility activity of the organosilicon compound administered orally for seven days prior to mating to proven breeder female mice.
  • mice A group of untreated female mice (Cox strain) were mated with a group of untreated male mice and animals which became pregnant and delivered an average normal litter in this first mating. Mice from this group were then selected as proven breeders for a second mating. These mice in the second mating were orally dosed (via gastric intubation) with either nothing, sesame oil, or two different doses (50 mgJkg. of body weight or 200 mgJkg. of body weight) of the organosilicon compound of the formula That which is claimed is:
  • a method for decreasing the reproductive function of mammals which comprises administering to a mammal an effective amount in the range of from 5 mg. to 200 mgJkg. of mammal body weight of an organosilicon compound of the formula alal a):

Abstract

thereby rendering the subject (either a male or female mammal) sterile.

A method for decreasing the reproductive function of mammals by administering a pharmacologically effective amount of a certain organosilicon compound. As a means of illustration, one can orally or parenterally administer an effective amount in the range of from 100 mg. to 5,000 mg. per kilogram of body weight (either as a single dose or as a daily dosage over a period of time) of an organosilicon compound of the formula

Description

United States Patent 191 Bennett et al.
1 1 Nov. 11,1975
[ METHOD FOR DECREASING THE REPRODUCTIVE FUNCTION OF MAMMALS [75] Inventors: Donald R. Bennett. Midland. Mich.;
James A. Mcllard. Gainesville. Fla.
1731 Assignee: Dow Corning Corporation, Midland.
Mich.
[2- Filed: Dec. 5. 1973 1211 Appl. No.:-121.893
Related US. Application Data [63] Continuation-impart of Ser. No. 837.922. June 30. 1969. Pat. No. 3.830.912. which is .1 continuation-in-part of Ser. No. 741.336. Jul) l. 1968. abandonedv [52] US. Cl. 424/184; 424/D1G. 12'. 424/D1G. 14 [51] Int. Cl.'- A61K 31/695 [58] Field of Search 424/184. DIG. l2. DIG. l4
[56] References Cited UNITED STATES PATENTS 2.934.472 1/1958 Ma) 424/184 3.382.150 9/1965 Grass 424/184 3.652.628 3/1972 Hyde et a1. 424/184 Primary Eruminer-Norman A. Drezin Attorney. Agem. ur FirmNorman E. Lewis 5 7 ABSTRACT Ha a al:
i-O- i thereby rendering the subject (either a male or female mammal) sterile.
6 Claims. No Drawings METHOD FOR DECREASING THE REPRODUCTIVE FUNCTION OF MAMMALS This application is a continuation-in-part of US. application, Ser. No. 837,922, filed June 30, 1969; now US. Pat. No. 3,830,912 which in turn is a continuationin-part of US. application Ser. No. 741,336, filed July 1, 1968', now abandoned.
This invention relates to a method for altering the reproductive function of mammals.
We have discovered that the administration of a pharmacologically effective amount of a certain organosilicon compound can alter the genital function (which includes reproductive capacity) of mammals. More precisely, a male mammal so treated exhibits depressant effects. For example, the sex accessory organos of the male (seminal vesicle, prostate) can be reduced in function and/or size and, with sufficient dosage, the male can also be rendered sterile as a result of depression of testes function. A female mammal so treated exhibits a decrease of fertility, i.e., the female mammals capability to conceive is inhibited with larger doses such that the female may be rendered sterile or abort if pregnant.
The principal object of this invention is to provide a therapeutically effective organosilicon compound which can render a male or female mammal sterile. Another principal object of this invention is to provide a method of administering an organosilicon compound which can be useful in the treatment of prostatic hypertrophy. It is still another object of this invention to pro vide a method of administering a certain organosilicon compound to females whereby the females capability to conceive or support and carry a living fetus through a normal pregnancy to a healthy birth can be inhibited. These and other attendant objects will become readily apparent from the detailed description which follows.
This invention relates to a method for decreasing the reproductive function of mammals which comprises administering an effective amount in the range of from 100 mg. to 5,000 mg./kg. of an organosilicon compound of the formula The organosilicon compound can be named as monophenylseptamethylcyclotetrasiloxane.
The organosilicon compound noted herein can be readily prepared by well known techniques described in the literature, e.g., by the cohydrolysis of chlorosilanes or by a suitable Grignard reaction.
The process of the present invention is operative on any mammal, e.g., rodents such as mice, rabbits and rats; domestic animals such as cats, swine, dogs, cattle, horses, and sheep; animals wild in nature such as deer, fox, wolves and lynx; and primates such as monkeys and man.
One can administer the organosilicon compound in any pharmacologically acceptable manner. They can be orally administered, parenterally administered or, in
2 certain species, topically administered. The parenteral mode of administration would, of course, include subcutaneous administration, intramuscular administration and the like.
It is of importance to note that the organosilicon compound described herein can be administered either in pure form in or combination with a pharmaceutically acceptable carrier or diluent. Suitable carriers include sesame oil, corn oil, mineral oil and other well known fat soluble carriers commonly employed in numerous pharmaceutical preparations.
As mentioned herein, the dose range of the organosilicon compound is in a pharmacologically effective amount. A dose range of from about mg. to about 5,000 mg. per kilogram of body weight has been found to be suitable; however, the precise dosage is ultimately dependent upon the mammal, the vehicle used, the route of administration, and the specific effects one wishes to achieve. The organosilicon compound may be administered as a single dose or it may be administered in daily dosage over varying periods of time, e.g., from about 7 to about 30 days or more.
The time required to achieve the desired effect is also variable, ranging anywhere from days to weeks or months, depending upon various factors, e.g., the species of mammal, dosage, route of administration, and the specific effect one wishes to achieve.
The particular alteration of the reproductive function which has been observed after administering the compound of the present invention to male mammals is a decrease in sex accessory organ function (decreased seminal fluid) and size (decreased seminal vesicle) with smaller doses of the compound and a decrease in prostatic or testicular function (decreased sperm count) or size with larger doses.
in view of the above, the method ofthis invention can be useful for decreasing the size of male sex accessory organs. In this regard, sex accessory organs are more sensitive than the testes to the organosilicon compound so that it is possible to decrease prostatic function and size without producing a significant effect on testicular size.
Furthermore, the method of this invention can be particularly useful for the treatment of prostatic hypertrophy. For example, by orally administering the compound of the formula at a daily (seven daily doses) dosage level of 100 mg. per kg. of body weight, it has been found that the prostate is significantly reduced in size.
If a high dosage level is maintained over a fairly long period of time in females prior to, during and/or following copulation, the anticipated embryo may fail to form or it may be resorbed by the female mammal.
It is also possible to prevent pregnancy (contraception) or abort pregnancy in female mammals because of an estrogenic depressant activity of certain of the organosilicon compound described herein.
In all of the foregoing cases, the pharmacological actions are reversible.
The following examples are illustrative only and should not be construed as limiting the invention which is properly delineated in the appended claims.
EXAMPLE I 4 for 3 days with autopsy of day four. The percent increase in uterine weight was determined between the control (sesame oil) and the treated animals. Table ll illustrates estrogen-like activity in the immature female 5 rat based upon percent increase in uterine weight. This example illustrates depressant activity of a certain Organosilicon compound in the male rat.
A group of male rats (Sprague Dawlcy strain) were TABLE H orally dosed via gastric intubation with an organosili- EstrogemLike Activity Ofit Certain Organosilicon con compound f h f l lO Compound in the Immature Female Rat Mean Uterine Weight (gm) Uterine O 100 gm Weight Dose final 92 Group mgJkg. n Body Weight ln- (CH3)1 i-O iC,,H l5 crease H Control (sesame oil) 6 6l .64
. (CH i- O- i(CH The animals were administered lOO mg./kg. of body a l 1 2 weight of the compound for a period of seven days with 20 autopsy on day eight. Final body weights were deter- FC'H 50 6 H718 mined in the fasted state just prior to sacrifice. Table 1 illustrates the depressant activity in the form of decreased seminal fluid, seminal vesicle and prostate (CH,),- i0 i-(CH,),* weights.
EXAMPLE 2 (CH,), i0 i c.ii, 200 s l76.93 I87" This example illustrates the estrogen-like activity of the Organosilicon compound in the immature female daily ommmingfma daywm autopsy on day Q rat. "p .0] compared to control.
TABLE I Depressant Activity of The Organosilicon Compound in the Male Rat Mean Mean Mean Mean Initial Final Seminal Seminal Mean Mean Body Body Fluid Vesicle Prostate Testes Weight Weight Ratio Ratio Ratio Ratio Group It (grams) (grams) :S.E. :S.E,, :S.E., fl.E.-,
Control (sesame oil) 10 380 384 .00264 .00158 .001 l9 .00905 :00020 100005 :00005 $00016 (i k), Halt i-O- i i-O- iC, H,, 10 381 37l .00115 .00i00 .0007! .00860 ,1, H, 1.00019" :OOOOS" :.00006*" 100018 ratio equals organ or fluid weight (gramsflfinal body weight (grams) "daily oral dosing of I00 mgJkg. of body weight for 7 days with autopsy on day 8. '"p .00] compared to control,
An immature female Wistar rat was orally adminis- 50 EXAMPLE 3 tered (via gastric intubation) either 50 mg./kg. of body weight or 200 mg./kg. of body weight of an orariosilicon compound of the formula TABLE "I Group Anti-Estrogen Activity of The Organosilicon Compound in the Immature Female Rat Organosilicon Mean Uterine Weight Dose (grams)ll00 grams mgJkg. n Final Body Weight (A) Control (sesame oil) (B) Estradial benzoate TABLE Ill-continued Anti-Estrogen Activity of The Organosilicon Compound in the Immature Female Rat Organosilicon Dose Mean Uterine Weight (gramsl/lOO grams Compound administered orally for three days with autopsy on day 4. Estradial benmate given subcutaneously in groups B. C and D.
EXAMPLE 4 Table IV illustrates the antifertility activity noted above.
TABLE IV Antifertility Activity of The Organosilicon Compound Administered Orally for Seven Days Prior to Mating to Proven Breeder Female Mice First Mating Second Mating Number Pregnant Mean Number Number Pregnant Mean Number Total Number Pups/Female Total Number Pups/Female (A) Control No Treatment 3/3 9.33 3/3 13.0 (B) Sesame Oil 3/3 10.33 3/3 12,0 (CH,)1 i-O- MCI-1,),
(CH,),- iO- i-(I-H (50 mgJltg.) (Cl-ldri-O-Ti-(Cm),
( H|); i-O- i-C.H,
(200 mgJkg.)
This example illustrates the antifertility activity of the organosilicon compound administered orally for seven days prior to mating to proven breeder female mice.
A group of untreated female mice (Cox strain) were mated with a group of untreated male mice and animals which became pregnant and delivered an average normal litter in this first mating. Mice from this group were then selected as proven breeders for a second mating. These mice in the second mating were orally dosed (via gastric intubation) with either nothing, sesame oil, or two different doses (50 mgJkg. of body weight or 200 mgJkg. of body weight) of the organosilicon compound of the formula That which is claimed is:
l. A method for decreasing the reproductive function of mammals which comprises administering to a mammal an effective amount in the range of from 5 mg. to 200 mgJkg. of mammal body weight of an organosilicon compound of the formula alal a):
i-O- l i-O- l-CH.
6. The method as recited in claim Sin which the carrier is sesame oil.

Claims (6)

1. A METHOD FOR DECREASING THE PRODUCTIVE FUNCTION OF MAMMALS WHICH COMPRISES ADMINISTERING TO A MAMMAL AN EFFECTIVE AMOUNT IN THE RANGE OF FROM 5 MG. TO 200 MG./KG. OF MAMMAL BODY WEIGH OF AN ORGANOSILICON COMPOUND OF THE FORMULA
2. The method as recited in claim 1 in which the depression of the reproductive function is the depression of the weight of male sex accessory glands.
3. The method as recited in claim 1 in which the depression of reproductive function is female antifertility.
4. The method as recited in claim 1 in which the organosilicon compound is administered orally.
5. The method as recited in claim 1 in which the organosilicon compound is administered in combination with a pharmaceutically acceptable carrier.
6. The method as recited in claim 5 in which the carrier is sesame oil.
US421893A 1969-06-30 1973-12-05 Method for decreasing the reproductive function of mammals Expired - Lifetime US3919417A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060291622A1 (en) * 2005-06-14 2006-12-28 L-3 Communications Security And Detection Systems, Inc. Inspection system with material identification

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2934472A (en) * 1958-01-13 1960-04-26 Dow Corning Process for relieving human gas pains with methylpolysiloxane
US3382150A (en) * 1962-05-01 1968-05-07 Smith Kline French Lab Spray-dried coated organopolysiloxane oral pharmaceutical or veterinary composition
US3652628A (en) * 1969-07-07 1972-03-28 Dow Corning Cyclotetrasiloxanes which impart alteration of genital function in mammals

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2934472A (en) * 1958-01-13 1960-04-26 Dow Corning Process for relieving human gas pains with methylpolysiloxane
US3382150A (en) * 1962-05-01 1968-05-07 Smith Kline French Lab Spray-dried coated organopolysiloxane oral pharmaceutical or veterinary composition
US3652628A (en) * 1969-07-07 1972-03-28 Dow Corning Cyclotetrasiloxanes which impart alteration of genital function in mammals

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060291622A1 (en) * 2005-06-14 2006-12-28 L-3 Communications Security And Detection Systems, Inc. Inspection system with material identification
US7653176B2 (en) * 2005-06-14 2010-01-26 L-3 Communications Security and Detection Systems Inc. Inspection system with material identification

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